Department of Veterinary Sciences, Laboratory of Cell Biology and Histology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.
Histochem Cell Biol. 2013 May;139(5):639-58. doi: 10.1007/s00418-013-1086-9. Epub 2013 Mar 17.
Mas-related gene (Mrg) receptors constitute a subfamily of G protein-coupled receptors that are implicated in nociception, and are as such considered potential targets for pain therapies. Furthermore, some Mrgs have been suggested to play roles in the regulation of inflammatory responses to non-immunological activation of mast cells and in mast cell-neuron communication. Except for MrgD, E and F, whose changed expression has been revealed during inflammation in the mouse intestine in our earlier studies, information concerning the remaining cloned mouse Mrg subtypes in the gastrointestinal tract during (patho) physiological conditions is lacking. Therefore, the present study aimed at identifying the presence and putative function of these remaining cloned Mrg subtypes (n = 19) in the (inflamed) mouse intestine. Using reverse transcriptase-PCR, quantitative-PCR and multiple immunofluorescence staining with commercial and newly custom-developed antibodies, we compared the ileum and the related dorsal root ganglia (DRG) of non-inflamed mice with those of two models of intestinal inflammation, i.e., intestinal schistosomiasis and 2,4,6-trinitrobenzene sulfonic acid-induced ileitis. In the non-inflamed ileum and DRG, the majority of the Mrg subtypes examined were sparsely expressed, showing a neuron-specific expression pattern. However, significant changes in the expression patterns of multiple Mrg subtypes were observed in the inflamed ileum; for instance, MrgA4, MrgB2and MrgB8 were expressed in a clearly increased number of enteric sensory neurons and in nerve fibers in the lamina propria, while de novo expression of MrgB10 was observed in enteric sensory neurons and in newly recruited mucosal mast cells (MMCs). The MrgB10 expressing MMCs were found to be in close contact with nerve fibers in the lamina propria. This is the first report on the expression of all cloned Mrg receptor subtypes in the (inflamed) mouse intestine. The observed changes in the expression and cellular localization of the Mrg subtypes suggest that these receptors are involved in the mediation of primary afferent responses, mast cell responses, and in neuroimmune communication during intestinal inflammation.
Mas 相关基因（Mrg）受体构成了 G 蛋白偶联受体家族的一个亚家族，该受体家族与痛觉有关，因此被认为是潜在的疼痛治疗靶点。此外，一些 Mrg 被认为在调节肥大细胞对非免疫性激活的炎症反应以及肥大细胞-神经元通讯中发挥作用。除了我们之前的研究中在小鼠肠道炎症中发现表达改变的 MrgD、E 和 F 之外，关于胃肠道中其余克隆的小鼠 Mrg 亚型在（病理）生理条件下的信息是缺乏的。因此，本研究旨在确定这些剩余克隆的 Mrg 亚型（n = 19）在（炎症）小鼠肠道中的存在和潜在功能。使用逆转录酶-PCR、定量-PCR 和用商业和新定制的抗体进行的多重免疫荧光染色，我们比较了非炎症性小鼠的回肠和相关的背根神经节（DRG）与两种肠道炎症模型，即肠道血吸虫病和 2,4,6-三硝基苯磺酸诱导的回肠炎。在非炎症性回肠和 DRG 中，大多数研究的 Mrg 亚型表达稀疏，表现出神经元特异性表达模式。然而，在炎症性回肠中观察到多个 Mrg 亚型的表达模式发生了显著变化；例如，MrgA4、MrgB2 和 MrgB8 在肠感觉神经元和固有层神经纤维中的表达明显增加，而 MrgB10 在肠感觉神经元和新招募的黏膜肥大细胞（MMC）中的表达则是新出现的。发现表达 MrgB10 的 MMC 与固有层中的神经纤维密切接触。这是第一个关于所有克隆的 Mrg 受体亚型在（炎症）小鼠肠道中的表达的报告。观察到的 Mrg 亚型表达和细胞定位的变化表明，这些受体参与了肠道炎症期间初级传入反应、肥大细胞反应和神经免疫通讯的介导。
